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Добірка наукової літератури з теми "Sterol metabolism"

Автор: Grafiati

Опубліковано: 21 червня 2022

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Статті в журналах з теми "Sterol metabolism"

Jing, Xiangfeng, and Spencer T. Behmer. "Insect Sterol Nutrition: Physiological Mechanisms, Ecology, and Applications." Annual Review of Entomology 65, no. 1 (January 7, 2020): 251–71. http://dx.doi.org/10.1146/annurev-ento-011019-025017.

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Insects, like all eukaryotes, require sterols for structural and metabolic purposes. However, insects, like all arthropods, cannot make sterols. Cholesterol is the dominant tissue sterol for most insects; insect herbivores produce cholesterol by metabolizing phytosterols, but not always with high efficiency. Many insects grow on a mixed-sterol diet, but this ability varies depending on the types and ratio of dietary sterols. Dietary sterol uptake, transport, and metabolism are regulated by several proteins and processes that are relatively conserved across eukaryotes. Sterol requirements also impact insect ecology and behavior. There is potential to exploit insect sterol requirements to ( a) control insect pests in agricultural systems and ( b) better understand sterol biology, including in humans. We suggest that future studies focus on the genetic mechanism of sterol metabolism and reverse transportation, characterizing sterol distribution and function at the cellular level, the role of bacterial symbionts in sterol metabolism, and interrupting sterol trafficking for pest control.

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Zhou, Wenxu, Paxtyn M. Fisher, Boden H. Vanderloop, Yun Shen, Huazhong Shi, Adrian J. Maldonado, David J. Leaver та W. David Nes. "A nematode sterol C4α-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity". Journal of Lipid Research 61, № 2 (23 вересня 2019): 192–204. http://dx.doi.org/10.1194/jlr.ra119000317.

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Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and Δ7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.

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Vidkjær, Nanna H., Karl-Martin V. Jensen, René Gislum, and Inge S. Fomsgaard. "Profiling and Metabolism of Sterols in the Weaver Ant Genus Oecophylla." Natural Product Communications 11, no. 1 (January 2016): 1934578X1601100. http://dx.doi.org/10.1177/1934578x1601100114.

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Sterols are essential to insects because they are vital for many biochemical processes, nevertheless insects cannot synthesize sterols but have to acquire them through their diet. Studies of sterols in ants are sparse and here the sterols of the weaver ant genus Oecophylla are identified for the first time. The sterol profile and the dietary sterols provided to a laboratory Oecophylla longinoda colony were analyzed. Most sterols originated from the diet, except one, which was probably formed via dealkylation in the ants and two sterols of fungal origin, which likely originate from hitherto unidentified endosymbionts responsible for supplying these two compounds. The sterol profile of a wild Oecophylla smaragdina colony was also investigated. Remarkable qualitative similarities were established between the two species despite the differences in diet, species, and origin. This may reflect a common sterol need/aversion in the weaver ants. Additionally, each individual caste of both species displayed unique sterol profiles.

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Gallagher, Patricia A., Steven A. Warner, and Aristotle J. Domnas. "Presqualene metabolism in two species of Lagenidium." Canadian Journal of Microbiology 40, no. 10 (October 1, 1994): 858–64. http://dx.doi.org/10.1139/m94-136.

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The fate of precursors of the isoprenoid pathway was studied in the sterol auxotroph Lagenidium giganteum and in the positive control organism Lagenidium callinectes. Acetate derived from glucose and mevalonic acid was converted to sterols and fatty acids in L. callinectes. Lagenidium giganteum converted mevalonic acid to sterols and fatty acids, but glucose-derived acetate was not utilized for sterol synthesis. The results showed that the defect in the isoprenoid pathway of L. giganteum occurs at the level of the β-hydroxy-β-methylglutarylcoenzyme A reductase–synthase complex. Various aspects of this defect are discussed relative to metabolism of the organism.Key words: Lagenidium giganteum, Lagenidium callinectes, glucose, mevalonic acid utilization, fatty acids, sterol production.

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Benveniste, Pierre. "Sterol Metabolism." Arabidopsis Book 1 (January 2002): e0004. http://dx.doi.org/10.1199/tab.0004.

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Tansley, Gavin, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, and Cheryl L. Wellington. "Sterol Lipid Metabolism in Down Syndrome Revisited: Down Syndrome Is Associated with a Selective Reduction in Serum Brassicasterol Levels." Current Gerontology and Geriatrics Research 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/179318.

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Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer’s Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population’s unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with DS compared to age-matched controls. Here we report that the levels of nearly all lipids and lipoproteins examined are similar to control subjects, suggesting that trisomy 21 does not lead to pronounced general alterations in sterol lipid metabolism. However, the levels of serum brassicasterol were markedly reduced in DS subjects.

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Whitaker, Bruce D. "LIPIDS IN SUBEPIDERMAL CORTICAL TISSUE OF `GOLDEN DELICIOUS' APPLE FRUIT." HortScience 30, no. 2 (April 1995): 191b—191. http://dx.doi.org/10.21273/hortsci.30.2.191b.

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Altered metabolism of membrane lipids has been proposed as a mechanism for the beneficial effects of postharvest calcium treatment on apple quality. A previous study showed that after transfer of apples stored 6 months at 0C to 20C, calcium-treated fruit exhibited slower loss of galactolipid and altered levels of sterol conjugates. The present study of lipids in “control” fruit was conducted as a prelude to further in-depth analyses of the effects of postharvest calcium and heat treatments on lipid metabolism in apples during and after cold storage. Neutral lipid, glycolipid (GL), and phospholipid (PL) fractions were obtained by column chromatography followed by TLC separation of GL and PL classes. The major GL were steryl glycosides (SG), acylated steryl glycosides (ASG), cerebrosides (CB), and mono- and digalactosyl diacylglycerols. Phosphatidylcholine (PC) > P-ethanolamine (PE) > P-irositol (PI) were the major PL. The fatty acids of PC and PE were quite similar, whereas those of PI were more saturated. CB included only 2-hydroxy fatty acids. Among the steryl lipids, free sterols > SG > ASG, with beta-sitosterol >90% of the total sterol in each.

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Najle, Sebastián R., María Celeste Molina, Iñaki Ruiz-Trillo, and Antonio D. Uttaro. "Sterol metabolism in the filasterean Capsaspora owczarzaki has features that resemble both fungi and animals." Open Biology 6, no. 7 (July 2016): 160029. http://dx.doi.org/10.1098/rsob.160029.

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Sterols are essential for several physiological processes in most eukaryotes. Sterols regulate membrane homeostasis and participate in different signalling pathways not only as precursors of steroid hormones and vitamins, but also through its role in the formation of lipid rafts. Two major types of sterols, cholesterol and ergosterol, have been described so far in the opisthokonts, the clade that comprise animals, fungi and their unicellular relatives. Cholesterol predominates in derived bilaterians, whereas ergosterol is what generally defines fungi. We here characterize, by a combination of bioinformatic and biochemical analyses, the sterol metabolism in the filasterean Capsaspora owczarzaki , a close unicellular relative of animals that is becoming a model organism. We found that C. owczarzaki sterol metabolism combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans. Moreover, we observe a differential transcriptional regulation of this metabolism across its life cycle. Thus, C. owczarzaki alternates between synthesizing 7-dehydrocholesterol de novo, which happens at the cystic stage, and the partial conversion—via a novel pathway—of incorporated cholesterol into ergosterol, the characteristic fungal sterol, in the filopodial and aggregative stages.

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Gylling, Helena, and Tatu A. Miettinen. "The effect of plant stanol- and sterol-enriched foods on lipid metabolism, serum lipids and coronary heart disease." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 42, no. 4 (July 1, 2005): 254–63. http://dx.doi.org/10.1258/0004563054255605.

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Phytosterols are plant sterols, mainly campesterol and sitosterol, and their respective stanols (5α-saturated derivatives), which chemically resemble cholesterol. They are present in a normal diet and are absorbed proportionally to cholesterol, but to a much lesser extent, such that less than 0.1% of serum sterols are plant sterols. Phytosterols inhibit intestinal cholesterol absorption, and fat-soluble plant stanol esters were introduced as a functional food for lowering serum cholesterol in the early 1990s; plant sterol esters entered the market at the end of the 1990s. Inhibition of the intestinal absorption of cholesterol stimulates cholesterol synthesis, a factor which limits serum cholesterol lowering to about 10% with phytosterols. Enrichment of the diet with plant stanol esters reduces absorption and serum concentrations of both cholesterol and plant sterols, whereas enrichment of the diet with plant sterol esters, especially in combination with statins, lowers serum cholesterol but increases serum plant sterol levels. Recent studies have suggested that high-serum plant sterol levels may be associated with increased coincidence of coronary heart disease. Estimates of coronary heart disease reduction by 20-25% with plant sterols/stanols is based mainly on short-term studies. Long-term cholesterol lowering, needed for the prevention of coronary heart disease, may be successful with plant stanol esters, which lower serum cholesterol in both genders over at least a year.

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Jaramillo-Madrid, Ana Cristina, Justin Ashworth, and Peter J. Ralph. "Levels of Diatom Minor Sterols Respond to Changes in Temperature and Salinity." Journal of Marine Science and Engineering 8, no. 2 (February 1, 2020): 85. http://dx.doi.org/10.3390/jmse8020085.

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Diatoms are a broadly distributed and evolutionarily diversified group of microalgae that produce a diverse range of sterol compounds. Sterols are triterpenoids that play essential roles in membrane-related processes in eukaryotic cells. Some sterol compounds possess bioactivities that promote human health and are currently used as nutraceuticals. The relationship between sterol diversity in diatoms and their acclimation to different environments is not well understood. In this study, we investigated the occurrence of different sterol types across twelve diatom species, as well as the effect of temperature reduction and changes in salinity on the sterol contents of three model diatom species. In the diatoms Thalassiosira pseudonana, Phaeodactylum tricornutum and Chaetoceros muelleri, we found that changes in the relative contents of minor sterols accompanied shifts in temperature and salinity. This may be indicative of acquired adaptive traits in diatom metabolism.

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Більше джерел

Дисертації з теми "Sterol metabolism"

Othman, Rgia Ali. "Assessment of sterol metabolism in sitosterolemia." Taylor & Francis, 2012. http://hdl.handle.net/1993/24317.

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Sitosterolemia (STSL) is a sterol storage disorder characterized by very high plasma plant sterol (PS) and 5α-stanol levels, and leads to premature atherosclerosis, xanthomas, macrothrombocytopenia and endocrine disruption. Ezetimibe (EZE), a sterol absorption inhibitor, reduces plasma PS levels in STSL but its effect on tissue pool of sterols has not been investigated yet. The research objectives were to assess if EZE reduces whole body sitosterol and cholesterol pool sizes, improves cholesterol homeostasis, enhance hematologic profile and reduce endocrine disruption in STSL. EZE effects on circulating levels of cholestanol and its precursors (cholesterol and bile acid derivative 7α-hydroxy-4-cholesten-3-one, 7α-H-C4) relative to exogenous stanols (sitostanol) were also studied. Eight STSL patients were taken off EZE for 14 wks. After 4 wks off EZE they received intravenous doses of D7-sitosterol and 18O-cholesterol for sterol pool sizes assessments, and oral doses of 13C-cholesterol and deuterium oxide to measure fractional cholesterol absorption and synthesis rates. EZE (10 mg/d) was resumed and stable isotopes testing repeated. Measurement parameters included isotopic sterol enrichments, blood cell count, plasma and red blood cell (RBC) PS, cholesterol and its precursor (lathosterol), 5α-stanols and plasma 7α-H-C4, and thyroid hormones levels. EZE reduced plasma levels of sitosterol and total cholesterol, whole body sitosterol and cholesterol pool sizes and fractional cholesterol absorption rate while increasing cholesterol synthesis, production and clearance rates. EZE increased platelet count and decreased platelet size without affecting RBC indices of size or mass. A substantial decrease in circulating sitostanol but moderate decrease of cholestanol was noted with EZE. EZE increased lathosterol but not 7α-H-C4, suggesting increases in cholesterol biosynthesis and thus precursor availability for synthesis of cholestanol. In summary, EZE reduces body stores of PS and cholesterol, and increases cholesterol turnover by reducing cholesterol absorption and enhancing its synthesis and clearance. EZE reduces circulating PS and 5α-stanol levels, and improves macrothrombocytopenia and thyroid disruption. Endogenous cholestanol in STSL is mainly derived from cholesterol but not bile acid synthesis pathway. These data suggest that EZE may reduce the risks of developing premature atherosclerosis, bleeding and hormone disruption, thereby reinforcing the rationale for the use of EZE in treatment of STSL.
February 2015

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Williams, Steven Geraint. "Factors influencing sterol metabolism in brewing yeasts." Thesis, University of Liverpool, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253296.

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Arnqvist, Lisa. "Plant sterol metabolism with emphasis on glycoalkaloid biosynthesis in potato /." Uppsala : Dept. of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/2007128.pdf.

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Wright, Edward A. "Studies on Sterol Metabolism in the Opportunistic Pathogen Pneumocystis carinii." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1367934810.

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Dahlin, Paul. "Analysis of sterol metabolism in the pathogenic oomycetes Saprolegnia parasitica and Phytophthora infestans." Doctoral thesis, Stockholms universitet, Institutionen för ekologi, miljö och botanik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-136551.

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Анотація:

The primary objective of this thesis was to investigate the sterol metabolism of two pathogenic oomycetes, specifically the processes of sterol synthesis and sterol acquisition in the fish pathogen Saprolegnia parasitica (Saprolegniales) and the plant pathogen Phytophthora infestans (Peronosporales). Furthermore, the effects of steroidal glycoalkaloids from Solanaceous plants, on P. infestans, were examined. The improved understanding of these processes should help to identify approaches for the identification of new oomycete inhibitors targeting sterol metabolism in agriculture and aquaculture farming systems, and to guide plant-breeding strategies to defend solanaceous plants against oomycetes. For these reasons, the molecular basis of the metabolic pathways of sterol synthesis and/or sterol acquisition was investigated. Sterols are derived from isoprenoids and indispensable in various biological processes. Our biochemical investigation of an oxidosqualene cyclase revealed that sterol synthesis in S. parasitica begins with the formation of lanosterol (Paper I), and a reconstruction of the complete sterol synthesis pathway to the final compound, fucosterol, in S. parasitica was performed using bioinformatics (Paper II). Complementary to this work, the extent to which P. infestans, which is incapable of de novo sterol synthesis, is able to modify exogenously provided sterols was investigated by determining the growth impact of various sterol supplements in the growth media (Paper II). Building on the sterol investigations, the solanaceous sterol derivatives from the glycoalkaloid family were analysed. These compounds contain both a steroidal and a carbohydrate (glycan) moiety. Data obtained by feeding various deuterium-labeled sterols to potato shoots, supported the theory that steroidal glycoalkaloids in Solanum tuberosum are produced from cholesterol (Paper III). Since these steroidal glycoalkaloids are thought to play a role in plant defense, their physiological effects on P. infestans were investigated (Paper IV). Unexpectedly we found that non-glycosylated steroidal alkaloids had a greater inhibitory effect than steroidal glycoalkaloids. Steroidal glycoalkaloids derived from other Solanaceous species exhibited different physiological effects on the growth of P. infestans. This research was conducted on two oomycete species belonging to the Saprolegniales and Peronosporales orders, hence the results presented are likely to be representative of each of these two oomycete orders.

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 4: Manuscript.

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Little, Marie-Térèse E. "The ontogeny of acyl coenzyme A: cholesterol acyltransferase in rat liver, intestine, adipose tissue, and aorta." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/29416.

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Epidemiological studies have shown that cholesterol is a major risk factor for the development of atherosclerosis. Since the atherosclerotic plaque develops over a long period interventions early in life may be of some benefit. In addition, it has been shown that the enzymes involved in cholesterol metabolism can be manipulated in early life. Therefore, studies of the developmental patterns of the key enzymes in cholesterol metabolism are of great importance. Acyl coenzyme A: cholesterol acyltransferase (ACAT) is the primary enzyme which catalyzes the conversion of free cholesterol to cholesterol esters in cells. A better understanding of the role and control of ACAT during development is needed in order to trace the possible causes in early life that lead to atherosclerosis in the adult. This research focused on the developmental pattern of ACAT in the rat liver, intestine, brown and white adipose tissue (BAT and WAT, respectively) and aorta. Age specific changes were observed in the rat liver, intestine and BAT. The rat liver and intestine possess significant amounts of ACAT activity throughout development and there appears to be marked variations in activity during this time. The rat BAT and WAT appear to be devoid of ACAT activity throughout development with the exception of adult BAT. Due to the small amount of the aortic tissue samples and/or the insensitivity of the assay, no definite conclusions could be made from this aortic study. In searching for factors that might control the ACAT enzyme the immediate effects of short-term manipulation of diet on the activity of ACAT were studied. The rats were all weaned early on day 18 to one of the following diets: Purina Rat Chow, high carbohydrate (HG) , high fat (HF) , or 2% cholesterol. The HF was the only diet that consistently increased hepatic ACAT activity in all the age groups. The cholesterol diets significantly increased the activity of ACAT in the 22 and 25 day old rats. The HG diet increased the activity of ACAT in the 22, 25, and 30 day old rats. No significant differences were observed between the adult control and HG diet groups. Feeding rats a HF or HG diet precipitated a dramatic drop in intestinal ACAT activity in the 22 day old animals. These effects were not observed in the older animals. The high cholesterol diet had no significant effect on the intestinal enzyme's activity in 22 day old rats. There was no significant change in the BAT and WAT ACAT activity with the experimental diets with the exception that all the experimental diets decreased ACAT activity in the adult BAT.
Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate

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Storey, Margo Kathleen. "Coordinate regulation of phosphatidylcholine, sphingomyelin, cholesterol and fatty acid metabolism in sterol regulatory defective Chinese hamster ovary cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ36563.pdf.

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Jain, Deepak M. "Effect of corn fibre oil and its constituents on cholesterol metabolism and intestinal sterol transporter gene expression in hamsters." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98732.

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The cholesterol-lowering effect of corn fiber oil, obtained from the seed coats of corn kernels, has been reported previously. Corn fiber oil contains phytosteryl fatty acyl esters, ferulate phytostanyl esters, and free phytosterols. To date, however, no studies have examined the cholesterol-lowering efficacy of ferulate phytostanyl esters. Moreover, although plant stanols and sterols have been established as cholesterol-lowering agents over the past five decades, their exact mechanisms of action are not clearly understood. One of the possible mechanism is that plant sterols/stanols disrupts the normal sub-cellular cholesterol absorption by down-regulation of the influx sterol transporters such as the Niemann pick C1 like 1(NPC1L1) protein and/or up-regulation of efflux sterol transporters such as the ATP binding cassette (ABC) G5 and ABCG8 protein. Hence, the objectives of this thesis were to assess the efficacy of corn fiber oil, ferulate phytostanyl esters and their parent compounds including sitostanol and ferulic acid, on plasma cholesterol levels. Further, objectives were to investigate their impact on parameters of cholesterol kinetics and gene expression of sterol transporters to obtain insight into their role in genetic control of regulation of cholesterol flux. Results of this experiment demonstrate that the hypocholesterolemic effect of corn fiber oil is mostly due to sitostanol, while esterification of ferulic acid and sitostanol yields no apparent synergistic cholesterol lowering effect. Present data exhibited a cholesterol absorption lowering effect of corn fiber oil and sitostanol and suggest that this effect may be due to up-regulation of intestinal enterocyte efflux sterol transporters such as ABCG5 and ABCG8.

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Winsor, Barbara. "Caracterisation de mutants de saccharomyces cerevisiae affectes dans la biosynthese des arn messagers rpobl, isel, rnal4, rnal5." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13216.

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Pons-Tostivint, Elvire. "Stratégies thérapeutiques innovantes pour stimuler la réponse immune antitumorale de cytotoxiques utilisés pour le traitement des cancers du sein." Thesis, Toulouse 3, 2021. http://www.theses.fr/2021TOU30216.

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Анотація:

Cette dernière décennie, de nombreuses données cliniques et pré-cliniques ont démontrées le rôle primordial du système immunitaire dans l'efficacité des chimiothérapies cytotoxiques. Ceci est lié, en partie, au déclenchement d'une mort cellulaire immunogène (MCI) par certains cytotoxiques, stimulant l'adjuvanticité des cellules tumorales. La MCI de la cellule tumorale est caractérisée par l'émission de signaux de dangers permettant de favoriser le recrutement et l'activation des cellules dendritiques, ainsi que la réponse immune antitumorale adaptative médiée par les lymphocytes T. La première étape de la MCI est l'exposition de la calréticuline à la face externe de la membrane plasmique, favorisant la phagocytose par les cellules dendritiques. Ensuite, les cellules tumorales sécrètent de l'ATP dans le milieu extra-cellulaire, par un mécanisme d'exocytose lysosomale dépendant de l'autophagie, favorisant le recrutement des cellules dendritiques. Enfin à un stade tardif, les cellules tumorales mourantes libèrent d'importantes quantité de protéines nucléaires dont l'HMGB1, ce qui entrainera la maturation des cellules dendritiques. Parmi les cancers du sein, le sous-type triple-négatif (TN) est le plus agressif, mais également le plus immunogène. Les patientes présentant un cancer du sein TN métastatique peuvent désormais bénéficier d'une combinaison de chimiothérapie et d'immunothérapie (avec un inhibiteur de checkpoint anti-PD-L1), même si les résultats présentés en septembre 2020 au congrès Européen de cancérologie (ESMO) remettent en cause l'efficacité de cette association. Malgré cette combinaison, la majorité des patientes rechuteront la première année. Le développement de thérapeutiques potentialisant la réponse immune est donc un enjeu majeur. La Dendrogénine A (DDA) est un métabolite suppresseur de tumeur caractérisé par l'équipe de Marc Poirot, avec une activité cytotoxique démontrée dans le cancer du sein hormono-dépendant, le mélanome et la leucémie aigüe myéloïde. La DDA induit une mort cellulaire par le déclenchement d'une autophagie dépendante de la voie du récepteur Liver-X-receptor (LXR) ß. Durant ma thèse, nous avons montré que la DDA exerçait une activité cytotoxique dans plusieurs lignées murines in vitro et in vivo, et une lignée humaine de cancer du sein TN in vitro. Nous avons montré que la DDA induisait des marqueurs d'autophagie dans ce modèle, in vitro et in vivo. Ensuite, nous avons montré qu'un traitement par DDA déclenchait les signaux de MCI sur deux lignées de cancer du sein TN (murine 4T1, et humaine MDA-MB-231), et une lignée murine de mélanome (B16F10). Les signaux de MCI induite par la DDA étaient supérieurs à ceux obtenus avec deux cytotoxiques standard, la doxorubicine et le mafosfamide. Nous avons enfin montré in vivo qu'une vaccination de souris immunocompétentes par des cellules mourantes traitées avec de la DDA, à partir de deux lignées cellulaires distinctes (4T1 et B16F10), induisait une protection prophylactique partielle lors du rechallenge de ces souris avec des cellules tumorales viables, en dehors de tout traitement systémique. Ces résultats nous montrent que la DDA pourrait être une nouvelle thérapeutique potentialisant la réponse immune antitumorale dans le cancer du sein TN
Last decade, several pre-clinical and clinical studies well demonstrated that the efficacy of conventional chemotherapies involves an immunological component. A part of the explanation comes from the demonstration that conventional chemotherapies can boost the adjuvanticity of cancer cells by inducing an immunogenic cell death (ICD). ICD of tumour cells drive an inflammatory response characterized by the activation of dendritic cells and the initiation of a cytotoxic T-lymphocyte immunity. During ICD, the reticulum endoplasmic stress promotes the translocation of the calreticulin protein to the cell surface, that facilitates the phagocytic uptake of tumour cells by immature dendritic cells. Then, the activation of autophagy in tumor cells induces the lysosomal secretion of ATP, that promotes the recruitment of dendritic cells. Lastly, dying cancer cells release a large amount of nuclear proteins including HMGB1, that drives the maturation of dendritic cells upon binding to TLR4. TNBC is defined as the most aggressive subtype of breast cancer, classified by its lack of expression of the hormonal receptor and the human epidermal growth factor receptor 2, but also considered as the most immunogenic subtype of breast cancer. A subset of TNBC patients are now eligible for immunotherapy in combination with chemotherapy, but all of them will finally relapse, mostly during the first year of treatment. Development of novel therapeutics to optimize immune response in these patients is urgently needed. Dendrogenin A has been characterized by the Marc Poirot's team as a tumour suppressor metabolite present in normal breast tissue, but absent in neoplastic breast tumour. DDA has an anti-tumour activity demonstrated in hormone-dependent breast cancer and melanoma cells, through the induction of an LXRß-dependent autophagy. During my thesis, we showed that DDA elicit cell death and autophagy in triple-negative breast cancer (TNBC) models in vitro and in vivo. Then, we demonstrated that DDA induced hallmarks of ICD in vitro in TNBC and melanoma cells lines. Indeed, we demonstrated that a treatment with DDA trigger (1) surface exposure of CALR, (2) release of ATP in the supernatant in an autophagy-dependent manner, and (3) release of HMGB1 in the supernatant. These danger signals were induced by DDA in a larger extent than doxorubicin and mafosfamide, described as two ICD-inducers. We then demonstrated in two different models that cancer cells undergoing ICD after being treated with DDA provide partial immune-mediated prophylactic protection against a subsequent challenge with living cancer cells of the same type. These results suggested that DDA could be a new therapeutic developed to potentiate antitumoral immune response in TNBC

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Книги з теми "Sterol metabolism"

G, Paumgartner, Stiehl A. 1941-, Gerok W. 1926-, and Bile Acid Meeting (8th : 1984 : Bern, Switzerland), eds. Enterohepatic circulation of bile acids and sterol metabolism: Proceedings of the 42nd Falk Symposium, held during the VIIIth International Bile Acid Meeting, Berne, August 31-Sept. 2, 1984. Lancaster: MTP Press, 1985.

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Ntambi, Ph.D., James M., ed. Stearoyl-CoA Desaturase Genes in Lipid Metabolism. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-7969-7.

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Symposium on Lipoprotein and Cholesterol Metabolism in Steroidogenic Tissues (1984 Laval University). Lipoprotein and cholesterol metabolism in steroidogenic tissues. Philadelphia: Georg F. Stickley Co., 1985.

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Steroid-protein interactions II. Berlin: Springer-Verlag, 1986.

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Cologne Workshop on Dope Analysis (10th 1992). 10th Cologne Workshop on Dope Analysis, 7th to 12th June 1992: Proceedings. Edited by Donike M. Köln: Sport und Buch Strauss, Edition Sport, 1993.

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S, Bhatt Tarlochan, ed. Cyclopenta(a)phenanthrenes: Polycyclic aromatic compounds structurally related to steroids. Cambridge [Cambridgeshire]: Cambridge University Press, 1987.

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Maximum muscle and minimum fat: The secret science behind physical transformation. Berkeley, Calif: North Atlantic Books, 2008.

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Freedman, Jeri. Steroids: High-risk performance drugs. New York: Rosen Pub. Group, 2009.

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International, Meeting on Steroids and the Nervous System (2nd 2003 Turin Italy). Steroids and the nervous system. New York: New York Academy of Sciences, 2003.

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International Meeting on Steroids and the Nervous System (2nd 2003 Turin, Italy). Steroids and the nervous system. New York: New York Academy of Sciences, 2003.

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Частини книг з теми "Sterol metabolism"

Rahier, Alain, Maryse Taton, and Sophie Pascal. "Plant Sterol Biosynthesis. Identification of the Component Reactions of Oxidative Sterol C4-Demethylation." In Plant Lipid Metabolism, 338–40. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-015-8394-7_92.

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Bouvier-Nave, Pierrette, Pascaline Ullmann, and Pierre Benveniste. "UDP-Glucose Sterol ß-Glucosyl Transferase, a Plant Sterol Conjugating Enzyme." In Enzymes of Lipid Metabolism II, 253–57. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5212-9_35.

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Gealt, Michael A., Brian E. Shapiro, Theresa A. Lindley, and Joseph L. Evans. "Sterol Metabolism in Aspergillus Species." In Aspergillus and Aspergillosis, 135–45. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4899-3505-2_13.

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Parks, Leo W., Thomas A. Lewis, Christopher Low, and Kristen Haeckler. "Effect of Intracellular Sterol Concentration on Sterol Esterification in Yeast." In The Metabolism, Structure, and Function of Plant Lipids, 57–61. Boston, MA: Springer New York, 1987. http://dx.doi.org/10.1007/978-1-4684-5263-1_8.

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Surjus, Agnès, Monique Durand, and Yves Sauvaire. "Effect of Salinity on the Sterol Content of Soybean Root Membranes." In Plant Lipid Metabolism, 344–46. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-015-8394-7_94.

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Hartmann, Marie-Andrée. "5 Sterol metabolism and functions in higher plants." In Lipid Metabolism and Membrane Biogenesis, 183–211. Berlin, Heidelberg: Springer Berlin Heidelberg, 2003. http://dx.doi.org/10.1007/978-3-540-40999-1_6.

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Patterson, Glenn W. "Sterol Synthesis and Distribution and Algal Phylogeny." In The Metabolism, Structure, and Function of Plant Lipids, 631–36. Boston, MA: Springer New York, 1987. http://dx.doi.org/10.1007/978-1-4684-5263-1_111.

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Lees, N. Douglas, and Martin Bard. "6 Sterol biochemistry and regulation in the yeast Saccharomyces cerevisiae." In Lipid Metabolism and Membrane Biogenesis, 213–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2003. http://dx.doi.org/10.1007/978-3-540-40999-1_7.

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Taton, Maryse, Florence Salmon, and Alain Rahier. "Plant Sterol Biosynthesis. Cytochrome P-450 Obtusifoliol 14α-Methyl Demethylase a Key Enzymatic Step." In Plant Lipid Metabolism, 341–43. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-015-8394-7_93.

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Svoboda, James A., and David J. Chitwood. "Inhibition of Sterol Metabolism in Insects and Nematodes." In ACS Symposium Series, 205–18. Washington, DC: American Chemical Society, 1992. http://dx.doi.org/10.1021/bk-1992-0497.ch015.

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Тези доповідей конференцій з теми "Sterol metabolism"

Sodi, Valerie L., Zachary Bacigalupa, Christina Ferrer, and Mauricio Reginato. "Abstract 1194: O-GlcNAcylation regulates breast cancer lipid metabolism via sterol regulatory element binding protein 1." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-1194.

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Nambiar, Dhanya K., Gagan Deep, Rana P. Singh, Chapla Agarwal, and Rajesh Agarwal. "Abstract 2452: Silibinin inhibits lipid metabolism by primarily targeting the master regulator sterol response element binding protein 1 (SREBP1) in prostate cancer cells." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-2452.

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shin, sangyun, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, and Young-Jin Chun. "Abstract LB-A12: New target for cancer metabolism : Steroid Sulfatase." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1535-7163.targ-15-lb-a12.

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Jovanović-Šanta, Suzana S., Aleksandar M. Oklješa, Antos B. Sachanka, Yaraslau U. Dzichenka, and Sergei A. Usanov. "17-SUBSTITUTED STEROIDAL TETRAZOLES – NOVEL LIGANDS FOR HUMAN STEROID-CONVERTING CYP ENZYMES." In 1st INTERNATIONAL Conference on Chemo and BioInformatics. Institute for Information Technologies, University of Kragujevac, 2021. http://dx.doi.org/10.46793/iccbi21.336js.

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In animal and human organisms, there are many enzymes, members of the family of heme- containing proteins, cytochromes P450 (CYPs), included in the biosynthesis and metabolism of many biomolecules, as cholesterol, bile acids, sex, and corticosteroid hormones, as well as in metabolism of drugs and xenobiotics. It is also well-known that different imidazole and triazole derivatives are efficient inhibitors of CYPs activity. In this study, we present in vitro screening of binding of novel androstane derivatives with tetrazole- containing substituents in position 17 to human recombinant steroid-converting CYP enzymes: CYP7A1, CYP7B1, CYP17A1, CYP19, and CYP21. Initial screening was performed using a high throughput screening approach, while the affinity of the ligands was analyzed using spectrophotometric titration. For some among tested compounds type I spectral response (substrate-like binding) for CYP7A1 selectively, while for one compound type II spectral response (inhibitor-like binding) for CYP21 were detected, with micromolar values of Kds. Interestingly, one compound with mixed spectral response was found to bind for CYP7B1, which means that there are two optimal positions of the ligand inside the protein active site. Such results could be useful in CYP-inhibiting drug development, during a fast, high-throughput screening of pharmacological potential of novel compounds, as well as in side- effects recognizing.

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Tang, Y. M., Y. X. Li, Z. Z. Tian, W. T. Liu, and D. G. Wang. "Water metabolism situation of steel workers in high temperature workplace." In International Conference on Environmental Science and Biological Engineering. Southampton, UK: WIT Press, 2014. http://dx.doi.org/10.2495/esbe140541.

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Michels, Kara A., Sally B. Coburn, Garnet Anderson, Louise A. Brinton, Chu Chen, Roni T. Falk, Margery L. Gass, et al. "Abstract PO029: Oral contraceptive use and postmenopausal sex steroid hormone metabolism." In Abstracts: AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; November 9-10, 2020. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1557-3265.endomet20-po029.

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Braadland, Peder Rustøen, Helene Hartvedt Grytli, Håkon Ramberg, Betina Katz, Lois Gauthier-Landry, Ralf Kellmann, Kurt Allen Krobert, et al. "Abstract A01: ADRB2 regulates phase II steroid metabolism and determines development of castration-resistant prostate cancer." In Abstracts: AACR Special Conference: Metabolism and Cancer; June 7-10, 2015; Bellevue, WA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1557-3125.metca15-a01.

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Luyimbazi, D., A. Akcakanat, L. Zhang, Y. Zheng, and F. Meric-Bernstam. "mTOR modulates cellular fat metabolism by regulating stearoyl-CoA desaturase 1 transcription." In CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-6030.

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Dasgupta, Subhamoy, Bin Zhang, Jean-Francois Louet, and Bert W. O'Malley. "Abstract 5153: Steroid receptor coactivator-2 mediates oncogenic reprogramming of cancer cell metabolism." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-5153.

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Kumari, Sonam, Sheema Khan, Mohammed Sikander, Shabnam Malik, Subhash C. Chauhan, and Meena Jaggi. "Abstract 4195: Steviol induces pancreatic cancer cell deathviatargeting glucose metabolism and protein translation pathways." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-4195.

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Звіти організацій з теми "Sterol metabolism"

Ginzberg, Idit, Richard E. Veilleux, and James G. Tokuhisa. Identification and Allelic Variation of Genes Involved in the Potato Glycoalkaloid Biosynthetic Pathway. United States Department of Agriculture, August 2012. http://dx.doi.org/10.32747/2012.7593386.bard.

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Steroidal glycoalkaloids (SGAs) are secondary metabolites being part of the plant defense response. The two major SGAs in cultivated potato (Solanum tuberosum) are α-chaconine and α-solanine, which exhibit strong cellular lytic properties and inhibit acetylcholinesterase activity, and are poisonous at high concentrations for humans. As SGAs are not destroyed during cooking and frying commercial cultivars have been bred to contain low levels, and their content in tubers should not exceed 20 mg/100 g fresh weight. However, environmental factors can increase tuber SGA content above the safe level. The focus of the proposed research was to apply genomic approaches to identify candidate genes that control potato SGA content in order to develop tools for potato improvement by marker-assisted selection and/or transgenic approaches. To this end, the objectives of the proposal included identification of genes, metabolic intermediates and allelic variations in the potato SGAbiosynthetic pathway. The SGAs are biosynthesized by the sterol branch of the mevalonic acid/isoprenoid pathway. Transgenic potato plants that overexpress 3-hydroxy-3-methylglutaryl-CoA reductase 1 (HMG1) or squalene synthase 1 (SQS1), key enzymes of the mevalonic acid/isoprenoid pathway, exhibited elevated levels of solanine and chaconine as well as induced expression of genes downstream the pathway. These results suggest of coordinated regulation of isoprenoid (primary) metabolism and SGA secondary metabolism. The transgenic plants were further used to identify new SGA-related candidate genes by cDNA-AFLP approach and a novel glycosyltransferase was isolated. In addition, genes involved in phytosterol biosynthesis may have dual role and synthesize defense-related steroidal metabolites, such as SGAs, via lanosterol pathway. Potato lanosterol synthase sequence (LAS) was isolated and used to prepare transgenic plants with overexpressing and silencing constructs. Plants are currently being analyzed for SGA content. The dynamics of SGA accumulation in the various organs of a potato species with high SGA content gave insights into the general regulation of SGA abundance. Leaf SGA levels in S. chacoense were 10 to 20-fold greater than those of S. tuberosum. The leptines, SGAs with strong antifeedant properties against Colorado potato beetles, were present in all aerial tissues except for early and mid-developmental stages of above ground stolons, and accounted for the high SGA content of S. chacoense. These results indicate the presence of regulatory mechanisms in most tissues except in stolons that limit the levels of α-solanine and α-chaconine and confine leptine accumulation to the aerial tissues. The genomes of cultivated and wild potato contain a 4-member gene family coding for SQS. Three orthologs were cloned as cDNAs from S. chacoense and heterologously expressed in E. coli. Squalene accumulated in all E. coli lines transformed with each of the three gene constructs. Differential transcript abundance in various organs and amino acid sequence differences in the conserved domains of three isoenzymes indicate subfunctionalization of SQS activity and triterpene/sterol metabolism. Because S. chacoense and S. phureja differ so greatly for presence and accumulation of SGAs, we selected four candidate genes from different points along the biosynthetic pathway to determine if chcor phuspecific alleles were associated with SGA expression in a segregating interspecific diploid population. For two of the four genes (HMG2 and SGT2) F2 plants with chcalleles expressed significantly greater total SGAs compared with heterozygotes and those with phualleles. Although there are other determinants of SGA biosynthesis and composition in potato, the ability of allelic states at two genes to affect SGA levels confirms some of the above transgenic work where chcalleles at two other loci altered SGA expression in Desiree. Present results reveal new opportunities to manipulate triterpene/sterol biosynthesis in more targeted ways with the objective of altering SGA content for both human health concerns and natural pesticide content without disrupting the essential metabolism and function of the phytosterol component of the membranes and the growth regulating brassinosteroids.

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Porat, Ron, Gregory T. McCollum, Amnon Lers, and Charles L. Guy. Identification and characterization of genes involved in the acquisition of chilling tolerance in citrus fruit. United States Department of Agriculture, December 2007. http://dx.doi.org/10.32747/2007.7587727.bard.

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Citrus, like many other tropical and subtropical fruit are sensitive to chilling temperatures. However, application of a pre-storage temperature conditioning (CD) treatment at 16°C for 7 d or of a hot water brushing (HWB) treatment at 60°C for 20 sec remarkably enhances chilling tolerance and reduces the development of chilling injuries (CI) upon storage at 5°C. In the current research, we proposed to identify and characterize grapefruit genes that are induced by CD, and may contribute to the acquisition of fruit chilling tolerance, by two different molecular approaches: cDNA array analysis and PCR cDNA subtraction. In addition, following the recent development and commercialization of the new Affymetrix Citrus Genome Array, we further performed genome-wide transcript profiling analysis following exposure to CD and chilling treatments. To conduct the cDNA array analysis, we constructed cDNA libraries from the peel tissue of CD- and HWB-treated grapefruit, and performed an EST sequencing project including sequencing of 3,456 cDNAs from each library. Based on the obtained sequence information, we chose 70 stress-responsive and chilling-related genes and spotted them on nylon membranes. Following hybridization the constructed cDNA arrays with RNA probes from control and CD-treated fruit and detailed confirmations by RT-PCR analysis, we found that six genes: lipid-transfer protein, metallothionein-like protein, catalase, GTP-binding protein, Lea5, and stress-responsive zinc finger protein, showed higher transcript levels in flavedo of conditioned than in non-conditioned fruit stored at 5 ᵒC. The transcript levels of another four genes: galactinol synthase, ACC oxidase, temperature-induced lipocalin, and chilling-inducible oxygenase, increased only in control untreated fruit but not in chilling-tolerant CD-treated fruit. By PCR cDNA subtraction analysis we identified 17 new chilling-responsive and HWB- and CD-induced genes. Overall, characterization of the expression patterns of these genes as well as of 11 more stress-related genes by RNA gel blot hybridizations revealed that the HWB treatment activated mainly the expression of stress-related genes(HSP19-I, HSP19-II, dehydrin, universal stress protein, EIN2, 1,3;4-β-D-glucanase, and SOD), whereas the CD treatment activated mainly the expression of lipid modification enzymes, including fatty acid disaturase2 (FAD2) and lipid transfer protein (LTP). Genome wide transcriptional profiling analysis using the newly developed Affymetrix Citrus GeneChip® microarray (including 30,171 citrus probe sets) revealed the identification of three different chilling-related regulons: 1,345 probe sets were significantly affected by chilling in both control and CD-treated fruits (chilling-response regulon), 509 probe sets were unique to the CD-treated fruits (chilling tolerance regulon), and 417 probe sets were unique to the chilling-sensitive control fruits (chilling stress regulon). Overall, exposure to chilling led to expression governed arrest of general cellular metabolic activity, including concretive down-regulation of cell wall, pathogen defense, photosynthesis, respiration, and protein, nucleic acid and secondary metabolism. On the other hand, chilling enhanced various adaptation processes, such as changes in the expression levels of transcripts related to membranes, lipid, sterol and carbohydrate metabolism, stress stimuli, hormone biosynthesis, and modifications in DNA binding and transcription factors.

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Fields, Michael, Mordechai Shemesh, Philip A. Fields, Anna-Riitta Fuchs, and Michael Diskin. Bovine Relaxin: A Placental Source and Effects on Prostaglandin and Steroid Metabolism. United States Department of Agriculture, January 1988. http://dx.doi.org/10.32747/1988.7568097.bard.

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Fields, Michael, Mordechai Shemesh, and Phillip A. Fields. Bovine Relaxin: A Placental Source and Effects on Prostaglandin and Steroid Metabolism. United States Department of Agriculture, December 1991. http://dx.doi.org/10.32747/1991.7594379.bard.

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Firon, Nurit, Prem Chourey, Etan Pressman, Allen Hartwell, and Kenneth J. Boote. Molecular Identification and Characterization of Heat-Stress-Responsive Microgametogenesis Genes in Tomato and Sorghum - A Feasibility Study. United States Department of Agriculture, October 2007. http://dx.doi.org/10.32747/2007.7591741.bard.

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Exposure to higher than optimal temperatures - heat-stress (HS) - is becoming increasingly common to all crop plants worldwide. Heat stress coinciding with microgametogenesis, especially during the post-meiotic phase that is marked by starch biosynthesis, is often associated with starch-deficient pollen and male sterility and ultimately, greatly reduced crop yields. The molecular basis for the high sensitivity of developing pollen grains, on one hand, and factors involved in pollen heat-tolerance, on the other, is poorly understood. The long-term goal of this project is to provide a better understanding of the genes that control pollen quality under heat-stress conditions. The specific objectives of this project were: (1) Determination of the threshold heat stress temperature(s) that affects tomato and sorghum pollen quality whether: a) Chronic mild heat stress conditions (CMHS), or b) Acute heat stress (AHS). (2) Isolation of heat-responsive, microgametogenesis-specific sequences. During our one-year feasibility project, we have accomplished the proposed objectives as follows: Objectrive 1: We have determined the threshold HS conditions in tomato and sorghum. This was essential for achieving the 2nd objective, since our accumulated experience (both Israeli and US labs) indicate that when temperature is raised too high above "threshold HS levels" it may cause massive death of the developing pollen grains. Above-threshold conditions have additional major disadvantages including the "noise" caused by induced expression of genes involved in cell death and masking of the differences between heatsensitive and heat-tolerant pollen grains. Two different types of HS conditions were determined: a) Season-long CMHS conditions: 32/26°C day/night temperatures confirmed in tomato and 36/26°C day maximum/night minimum temperatures in sorghum. b) Short-term AHS: In tomato, 2 hour exposure to 42-45°C (at 7 to 3 days before anthesis) followed by transfer to 28/22±2oC day/night temperatures until flower opening and pollen maturation, caused 50% reduced germinating pollen in the heat-sensitive 3017 cv.. In sorghum, 36/26°C day/night temperatures 10 to 5 days prior to panicle emergence, occurring at 35 days after sowing (DAS) in cv. DeKalb28E, produced starch-deficient and sterile pollen. Objective 2: We have established protocols for the high throughput transcriptomic approach, cDNA-AFLP, for identifying and isolating genes exhibiting differential expression in developing microspores exposed to either ambient or HS conditions and created a databank of HS-responsivemicrogametogenesis-expressed genes. A subset of differentially displayed Transcript-Derived Fragments (TDFs) that were cloned and sequenced (35 & 23 TDFs in tomato and sorghum, respectively) show close sequence similarities with metabolic genes, genes involved in regulation of carbohydrate metabolism, genes implicated in thermotolerance (heat shock proteins), genes involved in long chain fatty acids elongation, genes involved in proteolysis, in oxidation-reduction, vesicle-mediated transport, cell division and transcription factors. T-DNA-tagged Arabidopsis mutants for part of these genes were obtained to be used for their functional analysis. These studies are planned for a continuation project. Following functional analyses of these genes under HS – a valuable resource of genes, engaged in the HS-response of developing pollen grains, that could be modulated for the improvement of pollen quality under HS in both dicots and monocots and/or used to look for natural variability of such genes for selecting heat-tolerant germplasm - is expected.

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Butler, Walter R., Uzi Moallem, Amichai Arieli, Robert O. Gilbert, and David Sklan. Peripartum dietary supplementation to enhance fertility in high yielding dairy cows. United States Department of Agriculture, April 2007. http://dx.doi.org/10.32747/2007.7587723.bard.

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Objectives of the project: To evaluate the effects of a glucogenic supplement during the peripartum transition period on insulin, hepatic triglyceride accumulation, interval to first ovulation, and progesterone profile in dairy cows. To compare benefits of supplemental fats differing in fatty acid composition and fed prepartum on hepatic triglyceride accumulation, interval to first ovulation, progesterone profile, and uterine prostaglandin production in lactating dairy cows. To assess the differential and carry-over effects of glucogenic and fat supplements fed to peripartum dairy cows on steroidogenesis and fatty acids in ovarian follicles. To determine the carry-over effects of peripartum glucogenic or fat supplements on fertility in high producing dairy cows (modified in year 3 to Israel only). Added during year 3 of project: To assess the activity of genes related to hepatic lipid oxidation and gluconeogenesis following dietary supplementation (USA only). Background: High milk yields in dairy cattle are generally associated with poor reproductive performance. Low fertility results from negative energy balance (NEBAL) of early lactation that delays resumption of ovarian cycles and exerts other carryover effects. During NEBAL, ovulation of ovarian follicles is compromised by low availability of insulin and insulin-like growth factor-I (IGF-I), but fatty acid mobilization from body stores is augmented. Liver function during NEBAL is linked to the resumption of ovulation and fertility: 1) Accumulation of fatty acids by the liver and ketone production are associated with delayed first ovulation; 2) The liver is the main source of IGF-I. NEBAL will continue as a consequence of high milk yield, but dietary supplements are currently available to circumvent the effects on liver function. For this project, supplementation was begun prepartum prior to NEBAL in an effort to reduce detrimental effects on liver and ovarian function. Fats either high or low in unsaturated fatty acids were compared for their ability to reduce liver triglyceride accumulation. Secondarily, feeding specific fats during a period of high lipid turnover caused by NEBAL provides a novel approach for manipulating phospholipid pools in tissues including ovary and uterus. Increased insulin from propylene glycol (glucogenic) was anticipated to reduce lipolysis and increase IGF-I. The same supplements were utilized in both the USA and Israel, to compare effects across different diets and environments. Conclusions: High milk production and very good postpartum health was achieved by dietary supplementation. Peripartum PGLY supplementation had no significant effects on reproductive variables. Prepartum fat supplementation either did not improve metabolic profile and ovarian and uterine responses in early lactation (USA) or decreased intake when added to dry cow diets (Israel). Steroid production in ovarian follicles was greater in lactating dairy cows receiving supplemental fat (unsaturated), although in a field trail fertility to insemination was not improved.

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